Kawasaki disease (mucocutaneous lymph node syndrome)

Version: 2.2
Published: 23 May 2017
Condition for which Ig has an established therapeutic role.

This medical condition has either been superseded or has become inactive
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Specific Conditions
  • Kawasaki disease
Indication for Ig Use
  • Early in Kawasaki disease to prevent coronary artery pathology.
Level of Evidence Clear evidence of benefit (Category 1)
Description and Diagnostic Criteria Kawasaki disease is an acute, febrile, multi-system disease of children and young infants often involving the coronary arteries. Coronary artery aneurysms may occur from the second week of illness during the convalescent stage.

The cause of the condition is unknown, but there is evidence that the characteristic vasculitis results from an immune reaction characterised by T-cell and macrophage activation to an unknown antigen, secretion of cytokines, polyclonal B-cell hyperactivity, and the formation of autoantibodies to endothelial cells and smooth muscle cells. It is likely that in genetically susceptible individuals, one or more uncharacterised common infectious agents, possibly with super-antigen activity, may trigger the disease.

Diagnosis
A diagnosis of Kawasaki disease is generally made if fever of four or more days’ duration is associated with at least four of the following changes, which often appear sequentially:
 
  • bilateral (non-purulent) conjunctival injection
  • changes of the mucous membranes of the upper respiratory tract and oropharynx, including diffuse redness of pharyngeal mucosa, dry fissured lips, red fissured lips, and/or ‘strawberry tongue’
  • changes of the extremities, including peripheral erythema, peripheral oedema, and subsequent periungual or more generalised desquamation
  • polymorphous rash
  • cervical lymphadenopathy.

A diagnosis of Kawasaki disease may be made if fever and fewer than four of the changes listed above are present where there is strong clinical suspicion of Kawasaki disease (refer to Newburger 2004). Between 10% and 20% of cases, particularly in younger infants, present with fever and fewer than four of the listed criteria. Expert advice should be sought.

Data support the use of intravenous immunoglobulin (IVIg) while there is ongoing inflammation (usually taken as ongoing fever or raised acute inflammatory markers). Prognosis is worse if IVIg is used 10 days post-onset, but should be used at any time if there is evidence of inflammation. Up to 15% of patients do not respond to initial IVIg therapy. Consensus is for re-treatment with 2 g/kg of IVIg before considering steroids.
Justification for Evidence Category One high-quality systematic review of 16 randomised controlled trials (RCTs) that showed that IVIg is of benefit in treating Kawasaki disease (Biotext 2004).
Diagnosis Requirements

A diagnosis must be made by an Immunologist, Rheumatologist, Paediatrician or an Intensivist.
Qualifying Criteria for Ig Therapy
Therapy should be initiated within 10 days of fever onset if possible; however, children who present after 10 days of fever still should be treated if fever or other signs of persistent inflammation are present.
 
  • Clinical diagnosis of Kawasaki disease has been made.
Review Criteria for Assessing the Effectiveness of Ig Use
  • Clinical response to Ig therapy.
Dose
  • Dose (IVIg) - 2 g/kg in a single dose over 10–12 hours. Re-treatment with 2 g/kg in a single dose may be given when there is ongoing inflammation.
  • Induction dose with impaired cardiac function (IVIg) - 2 g/kg in a divided dose.
Dosing above 1g/kg per day is contraindicated for some IVIg products

The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.

Refer to the current product information sheet for further information.
Bibliography
Biotext 2004, ‘Summary data on conditions and papers’, in A systematic literature review and report on the efficacy of intravenous immunoglobulin therapy and its risks, commissioned by the National Blood Authority on behalf of all Australian Governments, pp. 255–6. Available from: http://www.nba.gov.au/pubs.htm [cited 7 Dec 2007]

Burns, JC & Glode, MP 2004, ‘Kawasaki syndrome’, Lancet, vol. 364, no. 9433, pp. 533–44.

De Zorzi, A, Colan, SD, Gauvreau, K, et al 1998, ‘Coronary artery dimensions may be misclassified as normal in Kawasaki disease’, Journal of Pediatrics, vol. 133, no. 2, pp. 254–8.

Durongpisitkul, K, Soongswang, J, Laohaprasitiporn, D, et al 2003, ‘Immunoglobulin failure and retreatment in Kawasaki disease’, Paediatric Cardiology, vol. 24, no. 2, pp. 145–8.

Feigin, RD, Cecchin, F & Wissman, SD 2006, ‘Kawasaki disease’, in JA McMillan (ed.), Oski’s paediatrics: principles and practice, 4th edn, Lippincott Williams & Wilkins, Philadelphia, pp. 1015–20.

Newburger, JW, Takahashi, M, Gerber, MA, et al 2004, ‘Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association’, Paediatrics, vol. 114, no. 6, pp. 1708–33.

Oates-Whitehead, RM, Baumer, JH, Haines, L, et al 2003, ‘Intravenous immunoglobulin for the treatment of Kawasaki disease in children (Cochrane Review)’, in The Cochrane Library, Issue 4, John Wiley & Sons, Ltd, Chichester, United Kingdom.

Rosenfeld, EA, Shulman, ST, Corydon, KE, et al 1995, ‘Comparative safety and efficacy of two immune globulin products in Kawasaki disease’, Journal of Paediatrics, vol. 126, no. 6, pp. 1000–3.

Stiehm, ER 2006, ‘Lessons from Kawasaki disease: all brands of IVIg are not equal’, Journal of Paediatrics, vol. 148, pp. 6–8.

Tsai, MH, Huang, YC, Yen, MH, et al 2006, ‘Clinical responses of patients with Kawasaki disease to different brands of intravenous immunoglobulin’, Journal of Paediatrics, vol. 148, no. 1, pp. 38–43.

Wang, CL, Wu, YT, Liu, CA, et al 2005, ‘Kawasaki disease: infection, immunity and genetics’, The Pediatric Infectious Disease Journal, vol. 24, no. 11, pp. 998–1004.